Fast, high-quality, and unshielded 0.2 T low-field mobile MRI using minimal hardware resources.

OBJECTIVE: To propose a deep learning-based low-field mobile MRI strategy for fast, high-quality, unshielded imaging using minimal hardware resources. METHODS: Firstly, we analyze the correlation of EMI signals between the sensing coil and the MRI coil to preliminarily verify the feasibility of active EMI shielding using a single sensing coil. Then, a powerful deep learning EMI elimination model is proposed, which can accurately predict the EMI components in the MRI coil signals using EMI signals from at least one sensing coil. Further, deep learning models with different task objectives (super-resolution and denoising) are strategically stacked for multi-level post-processing to enable fast and high-quality low-field MRI. Finally, extensive phantom and brain experiments were conducted on a home-built 0.2 T mobile brain scanner for the evaluation of the proposed strategy. RESULTS: 20 healthy volunteers were recruited to participate in the experiment. The results show that the proposed strategy enables the 0.2 T scanner to generate images with sufficient anatomical information and diagnostic value under unshielded conditions using a single sensing coil. In particular, the EMI elimination outperforms the state-of-the-art deep learning methods and numerical computation methods. In addition, 2 × super-resolution (DDSRNet) and denoising (SwinIR) techniques enable further improvements in imaging speed and quality. DISCUSSION: The proposed strategy enables low-field mobile MRI scanners to achieve fast, high-quality imaging under unshielded conditions using minimal hardware resources, which has great significance for the widespread deployment of low-field mobile MRI scanners.

Optimization design of a permanent magnet used for a low field (0.2 T) movable MRI system.

OBJECTIVE: To design a lightweight permanent magnet for a lowfield movable head imaging MRI system. MATERIALS AND METHODS: To reduce the weight of the magnet, the pole pieces, anti-eddy current plates, and shimming rings were removed, and the distance between the two vertical yokes was shortened as much as possible. To compensate for the magnetic field deformation caused by the shortened distance between two vertical iron yokes, two side magnetic poles were added to the vertical yokes. The magnetic field distributions in magnetic poles, the iron yoke, and the spherical imaging region were simulated. Phantom and in vivo head imaging were conducted with a lowfield movable MRI prototype scanner equipped with the proposed permanent magnet. RESULTS: A permanent magnet with a center field of 0.19815 T, a homogeneity of 46 ppm over the 20 cm spherical imaging region, and a weight of 654 kg have been achieved. Acceptable images of a phantom and a human brain have been acquired with the prototype MRI scanner. DISCUSSION: The proposed permanent magnet design significantly reduces the magnet's weight compared with the conventional magnet structure and shows promise in promoting the development of lowfield compact MRI systems.

Effect of aquaporin 4 protein overexpression in nigrostriatal system on development of Parkinson's disease.

OBJECTS: Recent studies indicated that aquaporin 4 (AQP4), as the main water channel in the central nervous system (CNS), participated in the onset and progression of Parkinson's disease (PD). But how the AQP4 influenced the exacerbation of PD has not been described in detail. In this study, the effect of the AQP4 protein overexpression in nigrostriatal system that include substantia nigra (SN) and striatum (CPu) on the development of PD was investigated. METHODS: Forty male Sprague Dawley rats were equally divided into two groups at random: PD group and control group, PD group undergoing surgery and receiving 6-hydroxydopamine (6-OHDA). Using MRI tracer-based method, extracellular space (ECS) diffusion parameters of nigrostriatal system for all rats were measured, including the clearance coefficient (k') and the half-life (t1/2). Immunohistochemistry of AQP4 was performed for 20 rats. RESULTS: The area of dark-stained AQP4 immunoreactivity increased markedly in SN of PD rats, there were significant differences between two groups (SN: t = 5.809, p < 0.0001; CPu: t = 5.943, p < 0.0001). And the diffusion parameters were significantly greater in PD group than that of control group, including k' (SN: t = 5.519, p < 0.0001; CPu: t = 2.149, p = 0.045) and t1/2 (SN: t = 6.131, p < 0.0001; CPu: t = 6.708, p < 0.0001). There was a significant positive correlation between the AQP4 expression level and the k' values (SN: r = 0.827, p = 0.0031; CPu: r = 0.641, p = 0.0046), and a significant negative correlation between AQP4 and the t1/2 values (SN: r=-0.654, p = 0.0403; CPu: r=-0.664, p = 0.0362). CONCLUSIONS: The results indicated that AQP4 expression was increased in nigrostriatal system of PD rats, therefore, the overexpression of AQP4 led to acceleration of the diffusion and drainage process of drugs in ECS, reduced the effect of drugs for the treatment of PD, inhibited the development of PD.

Identifying Wild Versus Cultivated Gene-Alleles Conferring Seed Coat Color and Days to Flowering in Soybean.

Annual wild soybean (G. soja) is the ancestor of the cultivated soybean (G. max). To reveal the genetic changes from soja to max, an improved wild soybean chromosome segment substitution line (CSSL) population, SojaCSSLP5, composed of 177 CSSLs with 182 SSR markers (SSR-map), was developed based on SojaCSSLP1 generated from NN1138-2(max)×N24852(soja). The SojaCSSLP5 was genotyped further through whole-genome resequencing, resulting in a physical map with 1366 SNPLDBs (SNP linkage-disequilibrium blocks), which are composed of more markers/segments, shorter marker length and more recombination breakpoints than the SSR-map and caused 721 new wild substituted segments. Using the SNPLDB-map, two loci co-segregating with seed-coat color (SCC) and six loci for days to flowering (DTF) with 88.02% phenotypic contribution were identified. Integrated with parental RNA-seq and DNA-resequencing, two SCC and six DTF candidate genes, including three previously cloned (G, E2 and GmPRR3B) and five newly detected ones, were predicted and verified at nucleotide mutant level, and then demonstrated with the consistency between gene-alleles and their phenotypes in SojaCSSLP5. In total, six of the eight genes were identified with the parental allele-pairs coincided to those in 303 germplasm accessions, then were further demonstrated by the consistency between gene-alleles and germplasm phenotypes. Accordingly, the CSSL population integrated with parental DNA and RNA sequencing data was demonstrated to be an efficient platform in identifying candidate wild vs. cultivated gene-alleles.

A transcriptomic analysis reveals soybean seed pre-harvest deterioration resistance pathways under high temperature and humidity stress.

Pre-harvest soybean seeds in the field are susceptible to high temperature and humidity (HTH) stress, leading to pre-harvest seed deterioration, which will result in a reduction in grain quality, yield, and seed vigor. To understand the gene expression involved in seed deterioration response under HTH stress, in this study, we conducted an RNA-Seq analysis using two previously screened soybean cultivars with contrasting seed deterioration resistance. HTH stress induced 1081 and 357 differentially expressed genes (DEGs) in the sensitive cultivar Ningzhen No. 1 and resistant cultivar Xiangdou No. 3, respectively. The majority of DEGs in the resistant cultivar were up-regulated, while down-regulated DEGs were predominant in the sensitive cultivar. KEGG pathway analysis revealed that metabolic pathways, biosynthesis of secondary metabolites, and protein processing in endoplasmic reticulum were the predominant pathways in both cultivars during seed deterioration under HTH stress. The genes involved in photosynthesis, carbohydrate metabolism, lipid metabolism, and heat shock proteins pathways might contribute to the different response to seed deterioration under HTH treatment in the two soybean cultivars. Our study extends the knowledge of gene expression in soybean seed under HTH stress and further provides insight into the molecular mechanism of seed deterioration as well as new strategies for breeding soybean with improved seed deterioration resistance.

Identifying a wild allele conferring small seed size, high protein content and low oil content using chromosome segment substitution lines in soybean.

KEY MESSAGE: A wild soybean allele conferring 100-seed weight, protein content and oil content simultaneously was fine-mapped to a 329-kb region on Chromosome 15, in which Glyma.15g049200 was predicted a candidate gene. Annual wild soybean characterized with small 100-seed weight (100SW), high protein content (PRC), low oil content (OIC) may contain favourable alleles for broadening the genetic base of cultivated soybeans. To evaluate these alleles, a population composed of 195 chromosome segment substitution lines (SojaCSSLP4), with wild N24852 as donor and cultivated NN1138-2 as recurrent parent, was tested. In SojaCSSLP4, 10, 9 and 8 wild segments/QTL were detected for 100SW, PRC and OIC, respectively. Using a backcross-derived secondary population, one segment for the three traits (q100SW15, qPro15 and qOil15) and one for 100SW (q100SW18.2) were fine-mapped into a 329-kb region on chromosome 15 and a 286-kb region on chromosome 18, respectively. Integrated with the transcription data in SoyBase, 42 genes were predicted in the 329-kb region where Glyma.15g049200 showed significant expression differences at all seed development stages. Furthermore, the Glyma.15g049200 segments of the two parents were sequenced and compared, which showed two base insertions in CDS (coding sequence) in the wild N24852 comparing to the NN1138-2. Since only Glyma.15g049200 performed differential CDS between the two parents but related to the three traits, Glyma.15g049200 was predicted a pleiotropic candidate gene for 100SW, PRC and OIC. The functional annotation of Glyma.15g049200 indicated a bidirectional sucrose transporter belonging to MtN3/saliva family which might be the reason that this gene provides a same biochemical basis for 100SW, PRC and OIC, therefore, is responsible for the three traits. This result may facilitate isolation of the specific gene and provide prerequisite for understanding the other two pleiotropic QTL.

Chromosome segment detection for seed size and shape traits using an improved population of wild soybean chromosome segment substitution lines.

Size and shape of soybean seeds are closely related to seed yield and market value. Annual wild soybeans have the potential to improve cultivated soybeans, but their inferior seed characteristics should be excluded. To detect quantitative trait loci (QTLs)/segments of seed size and shape traits in annual wild soybean, its chromosome segment substitution lines (CSSLs) derived from NN1138-2 (recurrent parent, Glycine max) and N24852 (donor parent, Glycine soja) and then modified 2 iterations (coded SojaCSSLP3) were improved further to contain more lines (diagonal segments) and less heterozygous and missing portions. The new population (SojaCSSLP4) composed of 195 CSSLs was evaluated under four environments, and 11, 13, 7, 15 and 14 QTLs/segments were detected for seed length (SL), seed width (SW), seed roundness (SR), seed perimeter (SP) and seed cross section area (SA), respectively, with all 60 wild allele effects negative. Among them, 16 QTLs/segments were shared by 2-5 traits, respectively, but 0-3 segments for each of the 5 traits were independent. The non-shared Satt274 and shared Satt305, Satt540 and Satt239 were major segments, along with other segments composed of two different but related sets of genetic systems for SR and the other 4 traits, respectively. Compared with the literature, 7 SL, 5 SW and 2 SR QTLs/segments were also detected in cultivated soybeans; allele distinction took place between cultivated and wild soybeans, and also among cultivated parents. The present mapping is understood as macro-segment mapping, the segments may be further dissected into smaller segments as well as corresponding QTLs/genes.

[Endovascular treatment in cerebral artery tandem lesions].

OBJECTIVE: To evaluate the effectiveness and safety of endovascular treatment in solving symptomatic cerebral artery tandem lesions. METHODS: From June 2012 to February 2014, 12 cases (24 lesions) with symptomatic cerebral artery tandem lesions were accepted for the endovascular treatment. The distributions of the tandem lesions were as follows: the common carotid artery and internal carotid artery (1 case), the internal carotid artery and the proximal of the carotid cavernous sinus segment (3 cases), the internal carotid artery and the distal of the carotid cavernous sinus segment (4 cases), the intracranial segment of internal carotid artery and middle cerebral artery M1 segment (2 cases), the first segment of vertebral artery and intracranial segment of vertebral artery (2 cases). All of these cases were treated from distal lesions to proximal lesions except for tandem lesions in the internal carotid artery and the distal of the carotid cavernous sinus segment in order to obtain better support. Tandem lesions were treated in the same operation with local anesthesia or general anesthesia. The procedures of the 12 cases retrospectively were analyzed and the peri-operation complications and responsibility region recurrent ischemic stroke incidents observed. RESULTS: All tandem lesions were solved successfully all at once. There were no peri-operation complications or recurrent ischemic stroke incidents. There were no recurrent ischemic stroke incidents or stent restenosis cases in the follow-up. CONCLUSION: It is safe and effective for selective endovascular treatment in solving symptomatic cerebral artery tandem lesions at the same time, but we should take careful preoperative evaluation and improve the operation plan.

[Morphological typing of the middle cerebral artery M1 segment by magnetic resonance angiography].

OBJECTIVE: To study the morphology of middle cerebral artery (MCA) M1 segment. METHODS: We selected the MRA data of 794 MCA (400 of the left side and 394 of the right side) from January 1, 2011 to June 30, 2011 consecutively and analyzed the morphology of the MCA M1 segment in axial, anteroposterior and lateral view, measured the length of the M1 segment, and analyzed the similarity of the left and right side M1 segment morphology. RESULTS: In axial, anteroposterior and lateral view, the MCA M1 segment showed C-shape > L-shape > S-shape. In axial view, it was about 373 (47%) M1 segment performance for the C-shape, of which 340 (42.8%) M1 segments showed bowing to the dorsal side, only 33 (4.2%) M1 segments showed bowing to the ventral side. In anteroposterior view, it was about 322 (40.6%) M1 segments of the performance of the C-shape, of which 262(33.0%) M1 segments showed a bowing to the superior, 60 (7.6%) showed bowing to the inferior. The similarity of the left and right MCA M1 segments was 27.2% (114/419) in axial view and 42.7% (179/419) in anteroposterior view. It was more similar in anteroposterior view than in axial view. Along with the increase of age, in the axial view, L-shape converted to C-shape very obviously, but only mildly elevated in S-shape. In anteroposterior view, the L-shape converted to the C-shape or S-shape along with the increase of age. CONCLUSION: The different morphology of MCA M1 segment in axial and anteroposterior view may be involved in the development of intracranial atherosclerosis.

[Related factors of hemodynamic damage after carotid artery stenting].

OBJECTIVE: To analyze correlation factors of hemodynamic damage after carotid artery stenting. METHODS: In this study, 66 cases (71 lesions) who undertook carotid artery stenting were collected and the correlation factors of hemodynamic damage were analyzed. RESULTS: Hemodynamic damage emerged in 23 cases (32.4%), of which, 11.3% developed hypotension. The distance between bifurcation and lesions (P=0.0020), plaque distribution (P=0.0002), plaque character (P=0.0019), post-dilation (P=0.0026) were associated with hemodynamic damage by single factor analysis. However, only eccentric plaque (P=0.0153) and calcified plaque (P=0.0097) were associated with hemodynamic damage by multiple factors analysis. All the patients could reach stable circulation by drugs during operation, and no cerebral ischemic events (transient ischemic attack or stroke) and cardiovascular ischemic events happened. CONCLUSION: The distance between bifurcation and lesions, eccentric plaques, calcified plaques are correlation factors of hemodynamic damage.

The three-dimensional shape analysis of the M1 segment of the middle cerebral artery using MRA at 3T.

INTRODUCTION: The M1 segment of the middle cerebral artery (MCA) is of great importance to neurosurgery and interventional radiology. The purpose of this study was to describe the M1 segment in three dimensions based on shape projection using magnetic resonance angiography (MRA). METHODS: A three-view method was established and used in the retrospective analysis of 717 M1 segments derived from 3D-TOF MRA images. In this method, the M1 segment was first projected on three orthogonal planes (axial, coronary, and sagittal plane); the courses of the projected vessels were classified as line-shape, C-shape, or S-shape on each orthogonal plane; and then the actual parameters, including internal diameter and so on, were measured on the projected images. The shape classifications and the measured parameters were efficient methods of describing the M1 segment. Twelve geometric models of the vessels were reconstructed and were compared with those from an actual validation method. RESULTS: The 3D shape of the M1 segment in the 3D orthogonal views was not uniform. Only 17.3 % M1 segments were straight, 43.5 % followed plane curves, and nearly 40 % were tortuous in 3D space. The probability distributions of shape classifications changed with age. The proportion of the tortuous vessels increased with age. We also showed that the three-view method is effective with a volume relative error of less than 13 %. CONCLUSION: The three-view method is convenient for describing the 3D morphology, including the shape information, of the M1 segment. It is a potential method for planning and predicting risk in neurosurgery/neurointervention.

[Clinical observation of middle cerebral artery angioplasty in treatment of subcortex cerebral watershed infarction with moderate or severe disabilities].

OBJECTIVE: To assess the safety and effectiveness of middle cerebral artery angioplasty in treatment of subcortical watershed infarcts (S-CWI) with moderate or severe disabilities. METHODS: From June 2011 to May 2012, 5 S-CWI patients (six lesions) with moderate or severe disabilities combining severe stenosis in Ipsilateral middle cerebral artery received middle cerebral artery angioplasty in Interventional Radiology and Vascular Surgery Department, Peking University Third Hospital. We observed the neurological score before and after angioplasty and assessed the improvement of neurological functions. RESULTS: The National Institute of Health stroke scale(NIHSS) scores were decreased by 4-6 points and modified Rankin scale(mRs) scores were decreased 1 point in 7 days. In the 3 months' follow-up, 4 patients' mRs scores were 1 point, and 1 patient's was 2 points. In the 1-year follow-up, there were no new strokes and instent restenosis events. CONCLUSION: Middle cerebral artery angioplasty in treatment of S-CWI with moderate or severe disabilities is beneficial.

Exploring Unlabeled Data in Multiple Aspects for Semi-Supervised MRI Segmentation.

Background: MRI segmentation offers crucial insights for automatic analysis. Although deep learning-based segmentation methods have attained cutting-edge performance, their efficacy heavily relies on vast sets of meticulously annotated data. Methods: In this study, we propose a novel semi-supervised MRI segmentation model that is able to explore unlabeled data in multiple aspects based on various semi-supervised learning technologies. Results: We compared the performance of our proposed method with other deep learning-based methods on 2 public datasets, and the results demonstrated that we have achieved Dice scores of 90.3% and 89.4% on the LA and ACDC datasets, respectively. Conclusions: We explored the synergy of various semi-supervised learning technologies for MRI segmentation, and our investigation will inspire research that focuses on designing MRI segmentation models.

Bidirectional, Multilayer MXene/Polyimide Aerogels for Ultra-Broadband Microwave Absorption.

To obtain high-performance electromagnetic microwave (EM) absorption materials with broad effective absorption bandwidth (EAB) and reduced thickness, designing structures has proved to be a promising way. Herein, ultra-broadband multilayer bidirectional MXene/polyimide EM absorption aerogels containing multi-structures on scales ranging from the micro- to the macroscale are produced with the aid of electric and temperature fields. On the microscale, under the action of electric force and temperature gradient, the ordered structures made of aligned Ti3C2Tx MXene nanosheets and the microscale layered aerogel walls enable the bidirectional aerogel to achieve a wide EAB of 8.58 GHz at a thickness of 2.1 mm. This is ascribed to the numerous aligned nanosheets and layered aerogel walls perpendicular to the incident EMs, facilitating the conversion of electromagnetic energy into electrical energy. Furthermore, on the macroscale, the multilayer bidirectional aerogel with non-gradient structures effectively resolves the conflict between impedance matching and energy loss, resulting in an ultrawide EAB of 9.41 GHz at a thickness of 3 mm. This innovative design of electric-field-assisted multilayer bidirectional aerogels with multiscale structural coupling may provide feasible and effective pathways for the development of advanced EM absorption materials.

[Quantitative calculation of drugs distribution parameter in the brain extracellular space by using MRI tracer].

OBJECTIVE: To build a mathematical model to simulate the drug distribution accompanying with diffusion, distribution and clearance in the brain extracellular space (ECS). METHODS: Magnetic resonance imaging (MRI) technology was used to monitor changes in the signal-intensity-related tracer gadolinium-diethylene triamine pentaacetic acidm(Gd-DTPA), as an external drug which was injected into the rat brain, and then the mathematical model was built by using the data to establish the diffusion, distribution and clearance process of Gd-DTPA in the brain ECS. The model equation was resolved by Laplace transform. In the sphere coordinates, the linear regressive model was adopted to obtain the estimation method of diffusion coefficient, clearance rate of drugs distribution in the brain ECS. RESULTS: The diffusion coefficient D and the clearance rate k were obtained as (2.73±0.364)×10(-4) mm(2)/s and (1.40±0.206)×10(-5) /s, respectively. CONCLUSION: The proposed method can accurately reflect the isotropic drug distribution in the brain ECS, and can serve as the foundation to further solve problems about the orthotropic distribution in the brain ECS.

Association between thyroid function and diabetes peripheral neuropathy in euthyroid type 2 diabetes mellitus patients.

Previous studies disclosed that a high thyroid stimulating hormone level is an independent risk factor for diabetes peripheral neuropathy (DPN) in subclinical hypothyroidism (SCH) patients with type 2 diabetes mellitus (T2DM). However, whether thyroid metabolism has an effect on DPN in euthyroid T2DM patients remains unknown. The aim of this study was to identify the association between thyroid function and DPN in euthyroid T2DM patients. A set of 580 euthyroid T2DM patients was enrolled in the current study and stratified into DPN and Non-DPN groups. Mann-Whitney U test was performed to analyze the continuous variables of biochemical and thyroid metabolism indicators, and the Chi-square test was used to compare the categorical variables. Spearman correlation analysis was performed to analyze the relationship between clinical indicators and free thyroxine (FT4). By using the logistic regression analysis, the prevalence of DPN in different thyroid function indicators were evaluated. T2DM patients with DPN had obviously lower levels of aspartate aminotransferase (AST), alpha-hydroxybutyric dehydrogenase (α-HBDH), superoxide dismutase (SOD), calcium (Ca), creatinine (Cr), uric acid (UA), retinol binding protein (RBP), total protein (TP), albumin (ALB), alanine aminotransferase (ALT) and FT4 than the T2DM patients without DPN (P < 0.05). FT4 was associated with TP, prealbumin (PA), ALB, SOD, anion gap (AG), Ca, chlorine (Cl), UA, RBP, apoprotein A (Apo A), apoprotein B (Apo B), apoprotein E (Apo E), and total cholesterol (TC). According to the FT4 quartile, participants were sequentially divided into four groups to compare the prevalence of DPN between each group. The data suggested that the prevalence of DPN in these four groups was 53.79%, 53.28%, 54.97%, 38.10%, respectively. Moreover, compared with quartile 4, patients in quartile 1, 2, 3 all had a significantly higher risk of DPN (P = 0.007, P = 0.011, P = 0.004). The level of FT4 was negatively correlated with the prevalence of DPN in euthyroid T2DM patients.

Thyroid-stimulating hormone within the normal reference range has a U-shaped association with the severity of coronary artery disease in nondiabetic patients but is diluted in diabetic patients.

Too high or too low thyroid-stimulating hormone (TSH) has been associated with the progress and prognosis of coronary artery disease (CAD). However, whether TSH within its normal reference range plays a role in the severity of CAD remains unclear. In this observational study, we explored the potential relationship of hypersensitive TSH (hs-TSH) with the severity of CAD in euthyroid patients with or without diabetes mellitus. A total of 7357 CAD patients with euthyroidism were enrolled in this study. Of those, 1997 had diabetes mellitus. The severity of CAD was evaluated through the presence of myocardial infarction (MI) and the severity of coronary lesions, which was calculated using the Gensini score (GS). Logistic regression models treating hs-TSH as a categorical variable and restricted cubic spline analyses treating it as a continuous variable were used to evaluate the associations of hs-TSH with the severity of CAD. The propensity score matching method was used to further validate the differences between diabetic and nondiabetic patients. CAD patients with diabetes mellitus had lower levels of hs-TSH (1.6 (0.97-2.53) vs 1.67 (1.00-2.64)) in serum compared with CAD patients without diabetes mellitus. Meanwhile, hs-TSH was independently related to the severity of CAD. In CAD patients with vs without diabetes mellitus, the U-shaped relationship between hs-TSH and MI was more prominent in patients without diabetes mellitus, and the significant U-shaped association between higher GS and hs-TSH remained only in nondiabetes. Therefore, hs-TSH within the normal reference range has a U-shaped association with the severity of CAD in nondiabetic patients, which is markedly diluted in diabetic patients.

Pin1 inhibitor API-1 sensitizes BRAF-mutant thyroid cancers to BRAF inhibitors by attenuating HER3-mediated feedback activation of MAPK/ERK and PI3K/AKT pathways.

BRAFV600E mutation is one of the most therapeutic targets in thyroid cancers. However, its specific inhibitors have shown little clinical benefit because they can reactivate the MAPK/ERK and PI3K/AKT pathways by feedback upregulating the transcription of HER3. Peptidyl-prolyl cis/trans isomerase Pin1 has been proven to be closely associated with tumor progression. Here, we aimed to determine antitumor activity of Pin1 inhibitor API-1 in thyroid cancer and its effect on cellular response to BRAF inhibitors. The results showed that API-1 exhibited strong antitumor activity against thyroid cancer. Meanwhile, it improved the response of BRAF-mutant thyroid cancer cells to BRAF inhibitor PLX4032 and there was a synergistic effect between them. Specially, a combination therapy of API-1 and PLX4032 significantly inhibited cell proliferation, colony formation, and the growth of xenograft tumors as well as induced cell apoptosis in BRAF-mutant thyroid cancer cells compared with API-1 or PLX4032 monotherapy. Similar results were also observed in transgenic mice with BrafV600E-driven thyroid cancer. Mechanistically, API-1 enhanced XPO5 ability to export pre-microRNA 20a (pre-miR-20a) from the nucleus to cytoplasm, thereby promoting the maturation of miR-20a-5p. Further studies showed that miR-20a-5p specifically targeted and down-regulated HER3, thereby blocking the reactivation of MAPK/ERK and PI3K/AKT signaling pathways caused by PLX4032. These results, taken together, demonstrate that Pin1 inhibitor API-1 significantly improves the sensitivity of BRAF-mutant thyroid cancer cells to PLX4032. Thus, this study not only determines the potential antitumor activity of Pin1 inhibitor API-1 in thyroid cancer but also offers an alternative therapeutic strategy for BRAF-mutant thyroid cancers by a combination of Pin1 inhibitor and BRAF kinase inhibitor.

Children's Dental Fear: Occurrence Mechanism and Prevention Guidance.

Children's dental fear (CDF) has become one of the main reasons affecting the quality of dental treatment. In order to reduce the incidence of CDF in China before and after children's dental visits, this review applies literature analysis and empirical summary methods to analyze and summarize academic discussions on this topic, including occurrence mechanism, prevention guidance, and the conclusion that the occurrence and prevention of CDF is closely related with children's internal characteristics and external influences. In the end, we propose a breakthrough of combining the CFSS-DS scale and three-grade prevention theory together in the future to provide new ideas and hypotheses for the prevention of CDF.

Epidural Pulsation Accelerates the Drainage of Brain Interstitial Fluid.

Unhindered transportation of substances in the brain extracellular space (ECS) is essential for maintaining brain function. Regulation of transportation is a novel strategy for treating ECS blockage-related brain diseases, but few techniques have been developed to date. In this study, we established a novel approach for accelerating the drainage of brain interstitial fluid (ISF) in the ECS using minimally invasive surgery, in which a branch of the external carotid artery is separated and implanted epidurally (i.e., epidural arterial implantation [EAI]) to promote a pulsation effect on cerebrospinal fluid (CSF) in the frontoparietal region. Tracer-based magnetic resonance imaging was used to evaluate the changes in ISF drainage in rats 7 and 15 days post-EAI. The drainage of the traced ISF from the caudate nucleus to ipsilateral cortex was significantly accelerated by EAI. Significant increases in the volume fraction of the ECS and molecular diffusion rate were demonstrated using the DECS-mapping technique, which may account for the mechanisms underlying the changes in brain ISF. This study provides a novel perspective for encephalopathy treatment via the brain ECS.